N. Azizi et al. / Tetrahedron Letters 45 (2004) 9233–9236
9235
Solid LiClO4
3. General procedure for the preparation of compounds 5
PhCHO + HN(SiMe3)2
Ph
NSiMe3
6
A mixture of aldehyde (10mmol), HMDS (18mmol)
and LiClO4 (20mmol) was heated for 15min at 50ꢁC,
then the reaction mixture was cooled to room tempera-
ture to give a solid crude product. LiClO4 was recovered
by filtration. The solvent was removed from the filtrate
under reduced pressure to give the crude product, which
was purified by recrystallization (cyclohexane, petro-
leum ether or ether). All compounds were characterized
1) TsOH, CH2Cl2
Ar
NH2
PhCHO
(R'O)3P
N
PO(OR')2
6
2) aq. NaOH
PO(OR')2
Ph
3
4
Ph
N
OSiMe3
6
6
+
PhCHO
7
Ph
Ph
N
N
- (SiMe3)2O
7
+
5a
1
Ph
Ph
Ph
on the basis of their spectroscopic data (IR, H NMR,
13C NMR, and MS) and by comparison with those
reported in the literature.12a,16,17
Scheme 3.
and a trialkyl phosphite gave compound 5 in low yields.
Finally, a one-pot reaction in the presence of TMSCl
gave an a-hydroxy phosphonate as the sole product.
With these results in hand, we suggest that the reaction
proceeds via an imine 6, as an intermediate. In the pres-
ence of trialkyl phosphite, 6 is converted into 4, which
after hydrolysis under acidic conditions gives a-amino
phosphonate 3. In the absence of trialkyl phosphite,
the intermediate 6 reacts with another molecule of alde-
hyde to form 7, and finally reaction of 7 and 6 yeilds 5,
as shown in Scheme 3.
References and notes
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Am. Chem. Soc. 1984, 106, 4282–4283.
In conclusion, in this study we have successfully
extended the use of HMDS as a source of ammonia
for the one-pot synthesis of a-amino phosphonates in
high yields under solvent-free conditions mediated by
solid LiClO4. The present procedure provides a novel,
very mild and green methodology for the preparation
of primary a-amino phosphonates as well as compound
5 under neutral reaction conditions.
5. (a) Chandrasekhar, S.; Prakash, S. J.; Jagadeshwar, V.;
Narsihmulu, Ch. Tetrahedron Lett. 2001, 42, 5561–5563;
(b) Yadav, J. S.; Reddy, B. V. S.; Sarita Raj, K.; Bhaskar
Reddy, K.; Prasad, A. R. Synthesis 2001, 2277–2280; (c)
Ranu, B. C.; Hajra, A.; Jana, U. Org. Lett. 1999, 1, 1141–
1143; (d) Qian, C.; Huang, T. J. Org. Chem. 1998, 63,
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Further investigation to broaden the scope and synthetic
applications of LiClO4 under solvent-free conditions is
underway in our laboratory
2. General procedure for the preparation of a-amino
phosphonates 3
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(b) Russell, G. A.; Yao, C.-F. J. Org. Chem. 1992, 57,
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12. (a) Soroka, M.; Kolodziejczyk, K. Tetrahedron Lett. 2003,
44, 1863–1865; (b) This experiment was carried out in our
laboratory with benzaldehyde, ammonia and trimethyl
phosphite in the presence of solid LiClO4 and under
various conditions.
A mixture of an aldehyde (5mmol), HMDS, (7mmol),
trialkyl phosphite (6mmol) and anhydrous LiClO4
(10mmol) was stirred at rt for about 15–45min. The
reaction was monitored by TLC. After completion of
the reaction, the product was extracted with CH2Cl2.
Then, p-toluenesulfonic acid monohydrate (6mmol)
was added, and the reaction mixture was stirred for
3h. Water was added and the solution neutralized with
NaOH (15%). The organic materials were extracted with
CH2Cl2 (2 · 10mL), and the combined organic layers
were washed with water (2 · 15mL), dried over anhy-
drous Na2SO4, and the solvent was removed under
reduced pressure. The crude product was purified by
column chromatography on silica gel (ethyl acetate,
petroleum ether, 10:90) to afford pure a-amino phos-
phonate. All compounds were characterized on the basis
13. (a) Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025–
1047; (b) Varma, R. S. Green Chem. 1999, 1, 43–55; (c)
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2978.
1
of their spectroscopic data (IR, H NMR, 13C NMR
and MS) and by comparison with those reported in
the literature.12,17
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14, 389–392; (b) Azizi, N.; Saidi, M. R. Tetrahedron Lett.